Clinical Trial 23220

• Overview

  Study Title:

  A Phase 1, Multicenter, Open-Label Study of REM-422, an MYB mRNA Degrader, in Patients With Relapsed/Refractory AML or Higher-Risk MDS

  Summary:

  This is a Phase 1, open-label, non-randomized, multicenter study investigating REM-422, a potent, selective, and oral small molecule mRNA degrader that reduces expression of the MYB transcription factor for patients with higher risk MDS or relapsed/refractory AML. This study includes a Dose Escalation Phase and a Dose Expansion Phase. The purpose of the Dose Escalation Phase is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of REM-422 in patients with higher risk MDS or relapsed/refractory AML. The purpose of Dose Expansion is to further evaluate the safety and anti-tumor activity of the RP2D carried forward from Dose Escalation.

  Objective:

  Primary objective: To evaluate the safety and tolerability of REM-422 in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or higher-risk (HR) myelodysplastic syndromes (MDS). Secondary objective: To evaluate preliminary antitumor activity of REM-422 in participants with R/R AML or HR-MDS. To characterize the pharmacokinetic (PK) profile of REM-422.

• Treatments

  Therapies:

  Therapy (NOS)

  Medications:

  REM-422 ()

• Inclusion Criteria

  Inclusion Criteria:
  • Participants must be able to provide informed consent.
  • Participants must be 18 or older at the time of informed consent.
  • Disease criteria: Histologically confirmed diagnosis of either: R/R AML, defined as relapse after transplantation, second or later relapse, refractory to initial induction or reinduction treatment or to initial treatment with hypomethylating (HMA)-based combinations, relapse after initial treatment, or otherwise considered relapsed or refractory in the opinion of the Investigator. High-risk and very-high-risk (VHR) MDS (higher-risk) per the International Prognostic Scoring System-Revised (IPSS-R) and/or International Prognostic Scoring System-Molecular (IPSS-M).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Has agreed to undergo serial blood and bone marrow sampling.
  • Participants must have completed systemic non-investigational therapy at least 14 days prior to initiating REM-422. Hydroxyurea is permissible for controlling peripheral leukemic blasts prior to enrollment and for up to 28 days following initiation of REM-422.
  • Toxicities from prior therapy must be either stable or recovered to Grade 1 or less.
  • Participants must be able to swallow and retain oral medications.
  • Oxygen saturation > 92% on room air or up to 2 L/min supplemental oxygen by nasal cannula with Grade 1 or less dyspnea.
  • People of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.
  • POCBP must agree to use acceptable, effective methods of contraception and not donate ova from screening until 6 months after discontinuation of REM-422. Women who have undergone surgical or ablative sterilization or who have been postmenopausal for 2 years or more are not considered to be of childbearing potential.
  • Men must agree to use acceptable, effective methods of contraception and must agree not to donate sperm from the start of receiving REM-422 until 6 months after discontinuation of REM-422.
  • Adequate organ function and laboratory parameters

• Exclusion Criteria

  Exclusion Criteria:
  • Active central nervous system (CNS) leukemia or a confirmed diagnosis of CNS leukemia.
  • Has undergone hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of REM-422 or is receiving immunosuppressive therapy post HSCT at the time of screening, or has GVHD requiring systemic treatment (topical steroids for ongoing skin GVHD is permitted).
  • Has immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
  • Known hypersensitivity or contraindication to any component of REM-422 or to drugs chemically related to REM-422 or its excipients.
  • Clinically significant active infection. Note: Patients with simple urinary tract infection or uncomplicated bacterial pharyngitis responding to active treatment are permitted. Note: Patients receiving intravenous (IV) antibiotics 7 days or less prior to enrollment are excluded (prophylactic antibiotics, antivirals, or antifungals are permitted).
  • Evidence of active HIV infection.
  • Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • Primary immunodeficiency.
  • Current or expected need for daily systemic corticosteroid therapy 10 mg or more of prednisone equivalent. Note: Patients who are receiving topical or inhaled corticosteroids with minimal systemic absorption are eligible for enrollment and may continue with minimal corticosteroid use as long as they are on a stable dose.
  • Live vaccine 6 weeks or less prior to the start of REM-422.
  • Use of strong CYP3A inhibitors (except azole antifungals) or CYP3A inducers
  • Drugs that reduce gastric acidity, such as H2-receptor antagonists (eg, ranitidine, famotidine) and proton pump inhibitors (eg, omeprazole, esomeprazole) within 7 days prior to the initiation of REM-422 administration or during the study.
  • Currently pregnant, have intentions to become pregnant during the study duration, or are currently lactating.
  • Has dysphagia, short-gut syndrome, gastroparesis, or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs.
  • Current use of prohibited medication 1 week or less before starting REM-422.
  • Clinically significant cardiovascular disease:
  • Has undergone major surgery (opening a mesenchymal barrier such as the pleural cavity, peritoneum, or meninges or surgical procedures requiring general anesthesia) > History of organ transplant that requires use of immunosuppressive agents.
  • History or current autoimmune disease requiring systemic treatment (eg, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus).
  • Radiation therapy 7 days or less prior to the start of REM-422.
  • Concurrent or previous other malignancy 2 years or less of enrollment, except curatively treated malignancies including basal or squamous cell skin cancer, breast cancer, prostate intraepithelial neoplasm, and carcinoma in situ of the cervix.
  • Receiving any other investigational treatment for any indication 3 weeks or less prior to enrollment.
  • Unwillingness or inability to follow protocol requirements.
  • Any condition that, in the opinion of the Investigator, would interfere with evaluation of REM-422 or interpretation of the participant's safety or study results.

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